Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC).
Tzur Alexander Mayer, Michael Alex Matar, Zeev Kaplan, Joseph Zohar, Hagit Cohen
Pharmacology, Biochemistry, and Behavior July 2014 DOI: 10.1016/j.pbb.2014.04.014 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Prospective animal model study Peer reviewed |
|---|---|
| Population | Rats exposed to predator scent stress |
| Interventions | Delta-9-tetrahydrocannabinol (Δ9-THC) AM251 |
| Dose | Δ9-THC 1, 5 and 10 mg/kg; AM251 dose not stated |
| Duration | Behavioral testing at 1, 6 and 24 h or 7 days after exposure, with trauma cue exposure on day 8; corticosterone assessed over 2 h after exposure |
| Measures | elevated plus-maze, acoustic startle response, freezing behavior, circulating corticosterone levels, pre-set cut-off behavioral criteria |
| Topics | Cannabis |
| Keywords | Animal model Cb1 antagonist/inverse agonist Delta-9-Tetrahydrocannabinol δ9-THC Early drug intervention Posttraumatic stress disorder Secondary prevention |
| Key points | A single early dose of Δ9-THC attenuated short-term (1–6 h) anxiety-like behavior but showed no effect on longer-term (7-day) PTSD-like behavioral stress responses or freezing to a trauma cue; it also decreased corticosterone. The CB1 antagonist/inverse agonist AM251, given 1 h after exposure, attenuated long-term behavioral stress responses through activation of the HPA axis. The authors argue that the lack of preventive efficacy of early Δ9-THC, plus reports of its anxiogenic effects in many individuals, raises doubts about its clinical value and the advisability of clinical trials. |
Abstract
The therapeutic value of Delta-9-tetrahydrocannabinol (Δ9-THC) in the aftermath of trauma has recently raised interest. A prospective animal model for posttraumatic stress disorder was employed to assess the behavioral effects of a single dose of Δ9-THC administered intraperitoneally following exposure to psychogenic stress. Animals were exposed to predator scent stress and treated 1h later with Δ9-THC (1, 5 and 10mg/kg) or vehicle. The outcome measures included behavior in an elevated plus-maze and acoustic startle response 1, 6 and 24 h or 7 days after exposure and freezing behavior upon exposure to a trauma cue on day 8. Pre-set cut-off behavioral criteria classified exposed animals as those with "extreme," "minimal" or "intermediate" (partial) response. Circulating corticosterone levels were assessed over 2h after exposure with and without Δ9-THC. The behavioral effects of a CB1 antagonist (AM251) administered systemically 1h post exposure were evaluated. In the short term (1-6 h), 5 mg/kg of Δ9-THC effectively attenuated anxiety-like behaviors. In the longer-term (7 days), it showed no effect in attenuating PTSD-like behavioral stress responses, or freezing response to trauma cue. Δ9-THC significantly decreased corticosterone levels. In contrast, administration of AM251 (a CB1 antagonist/inverse agonist) 1 h post exposure attenuated long-term behavioral stress responses through activation of the HPA-axis. The demonstrated lack of preventive efficacy of early Δ9-THC treatment and reports of its anxiogenic effects in many individuals raises doubts not only regarding its potential clinical value, but also the advisability of clinical trials. The endocannabinoids exert complex effects on behavioral responses mediating glucocorticoid effects on memory of traumatic experiences.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 2
Cites 4
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